Targeting cyclin dependent kinases in management of human cancer

Uncontrolled proliferation is the hall mark of cancer and abnormal cell cycle regulation in cancer. CDK plays very important role in the control of the cell cycle and its proliferation. CDK2 is the “superstar” among the CDK family. CDK2 has cyclin A and cyclin E in its complex which the cyclin A complex require to progress through S phase regulated by phosphorylation and cyclin E require to transition from the G1 to S phase in cell cycle. Also, the mechanism of binding of CDK2 with its inhibitors as well as the changes of binding mechanisms following conformational variation of CDK2 are compared. Considering this fact, inhibition or disruption of the CDK2/cyclin complexes should be possible to suppress the hyper activation of CDK2 and hold back the infinite cell proliferation. There are main four binding site of CDK inhibitors. Competitive binding sites (site 1), Noncompetitive binding sites (site 2 and 3), Allosteric binding site (site 4). CDK inhibitors are mainly used in cancers including leukemia, melanoma, solid tumors and other types are being targeted.